Mechanism of biosynthesis of long chain alkanes, alkane diols, 3- hydroxy acids, methyl-branched acids, erythronolide, and wax esters will be elucidated by purification and characterization of the relevant enzymes from meibomian glands, harderian glands, uropygial glands, Mycobacterium tuberculosis bovis, Streptomyces erythreus, Euglena gracilis and Pisum sativum. The structural relationship between fatty acid synthase and chain-elongating mycocerosic acid synthase will be established by cloning and sequencing their genes from M. bovis. The mechanism of interaction between fatty acid synthase and S-acyl fatty acid synthase thioesterase will be elucidated by chemical modification and fluorescence energy transfer. Structures of cDNA and the genes for S-acyl fatty acid synthase thioesterase, the thioesterase domain of fatty acid synthase and thioesterase B from mallard ducks will be determined to elucidate the structural and functional relationships among thioesterases. The role of peroxisomes in the production of sebaceous gland lipids will be elucidated. The mechanism of hormonal induction of peroxisome proliferatopm om the sebacceous glands will be elucidated one or two peroxisomal enzymes that are highly induced in the duck uropygial glands will be purified and their cDNA and genes will be cloned. The mechanism of hormonal stimulation of these genes and suppression of the thioesterase gene by estrogen will be studied. Structure of malonyl-CoA decarboxylase from Streptomyces erythreus and goose uropygial gland will be determined by nucleotide sequencing of cloned DNA. The structure and mechanism of tissue specific expression of malonyl- CoA decarboxylase gene will be elucidated and the mechanisms by which this normally mitochondrial enzyme is made to accumulate int he cytoplasm of the goose uropygial gland will be elucidated. The mechanism and regulation of biosynthesis of the above natural products are known to be relevant to a variety of health problems from acne to cancer and the proposed research is expected to fill major gaps in our knowledge of this area.